The major objective of this research is to make significant contributions to organic chemistry and medicine through studies directed towards the synthesis of natural products with antitumor activity or tumor-promoting activity, including halichondrins, C-indolactam V, cytoblastin, taxol/cephalomannine, mycalamides/onnamide, and daunomycin analogs. We believe that the power of organic chemistry, especially organic synthesis, is most effectively extended by challenging complex systems, and much of the progress of medicine certainly depends upon extension of the power of chemistry. More specifically, research efforts will be made first to develop general, flexible, and efficient syntheses of certain natural products and then to apply these to the synthesis of their analogs and derivatives, whose study will provide clues for developing better antitumor drugs or for understanding the tumor-promoting process. Among the five programs proposed, the halichondrin project is most advanced in our quest for an antitumor drug, and research plans are presented to identify a drug candidate for further clinical development.